The present invention relates to a wearable tissue spectrophotometer for in vivo examination of tissue of a specific target region.
Continuous wave (CW) tissue oximeters have been widely used to determine in vivo concentration of an optically absorbing pigment (e.g., hemoglobin, oxyhemoglobin) in biological tissue. The CW oximeters measure attenuation of continuous light in the tissue and evaluate the concentration based on the Beer Lambert equation or modified Beer Lambert absorbance equation. The Beer Lambert equation (1) describes the relationship between the concentration of an absorbent constituent (C), the extinction coefficient (xcex5), the photon migration pathlength  less than L greater than , and the attenuated light intensity (I/Io).                                           log            ⁡                          [                              I                /                                  I                  o                                            ]                                             less than             L             greater than                           =                  ∑                                    ε              i                        ⁢                          C              i                                                          (        1        )            
The CW spectrophotometric techniques can not determine xcex5, C, and  less than L greater than  at the same time. If one could assume that the photon pathlength were constant and uniform throughout all subjects, direct quantitation of the constituent concentration (C) using CW oximeters would be possible.
In tissue, the optical migration pathlength varies with the size, structure, and physiology of the internal tissue examined by the CW oximeters. For example, in the brain, the gray and white matter and the structures thereof are different in various individuals. In addition, the photon migration pathlength itself is a function of the relative concentration of absorbing constituents. As a result, the pathlength through an organ with a high blood hemoglobin concentration, for example, will be different from the same with a low blood hemoglobin concentration. Furthermore, the pathlength is frequently dependent upon the wavelength of the light since the absorption coefficient of many tissue constituents is wavelength dependent. Thus, where possible, it is advantageous to measure the pathlength directly when quantifying the hemoglobin concentration in tissue.
In one aspect, the present invention is a pathlength corrected oximeter that utilizes principles of continuous wave spectroscopy and phase modulation spectroscopy. The oximeter is a compact unit constructed to be worn by a subject on the body over long periods of activity. The oximeter is also suitable for tissue monitoring in critical care facilities, in operating rooms while undergoing surgery or in trauma related situations.
The oximeter is mounted on a body-conformable support structure placed on the skin. The support structure encapsulates several light emitting diodes (LEDs) generating light of different wavelengths introduced into the examined tissue and several photodiode detectors with interference filters for wavelength specific detection. Since both the LEDs and the photodiodes are placed directly on the skin, there is no need to use optical fibers. The distance between the LEDs and the diode detectors is selected to examine a targeted tissue region. The support structure also includes a conformable barrier, located between the LEDs and the diode detectors, designed to reduce detection of light that migrates subcutaneously from the source to the detector. The support structure may further include means for preventing escape of photons from the skin without being detected; the photon escape preventing means are located around the LEDs and the photodiode detectors.
The LEDs, the diode detectors, and the electronic control circuitry of the oximeter are powered by a battery pack adapted to be worn on the body or by the standard 50/60 Hz supply. The electronic circuitry includes a processor for directing operation of the sources, the detectors and for directing the data acquisition and processing. The data may be displayed on a readout device worn by the user, sent by telemetry to a remote location or accumulated in a memory for later use.
The oximeter is adapted to measure the attenuation of light migrating from the source to the detector and also to determine the average migration pathlength. The migration pathlength and the intensity attenuation data are then used for direct quantitation of a tissue property.
In another aspect, the invention is a spectrophotometer for tissue examination utilizing a measured average pathlength of migrating photons, including an oscillator adapted to generate a carrier waveform of a selected frequency comparable to an average migration time of photons scattered in tissue on paths from an optical input port to an optical detection port; a light source, operatively connected to the oscillator, adapted to generate light of a selected wavelength that is intensity modulated at the frequency and introduced to a subject at the input port; a photodiode detector adapted to detect, at the detection port, light of the selected wavelength that has migrated in the tissue of the subject between the input and detection ports; a phase detector, operatively connected to receive signals from the oscillator and the diode detector, adapted to measure a phase shift between the introduced and the detected light; and a processor adapted to calculate pathlength based on the phase shift, and determine a physiological property of the examined tissue based on the pathlength.
In another aspect, the invention is a spectrophotometer for tissue examination utilizing a measured average pathlength of migrating photons, including an oscillator adapted to generate a carrier waveform of a selected frequency comparable to an average migration time of photons scattered in tissue on paths from an optical input port to an optical detection port; a light source, operatively connected to the oscillator, adapted to generate light of a selected wavelength that is intensity modulated at the frequency and introduced to a subject at the input port; a photodiode detector adapted to detect, at the detection port, light of the selected wavelength that has migrated in the tissue of the subject between the input and detection ports; a phase splitter adapted to produce, based on the carrier waveform, first and second reference phase signals of predefined substantially different phase; first and second double balanced mixers adapted to correlate the reference phase signals and signals of the detected radiation to produce therefrom a real output signal and an imaginary output signal, respectively; and a processor adapted to calculate, on the basis of the real output signal and the imaginary output signal, a phase shift between the introduced light and the detected light, and determine a physiological property of the examined tissue based on the phase shift.
In another aspect, the invention is a spectrophotometer for tissue examination utilizing a measured average pathlength of migrating photons, comprising a first oscillator adapted to generate a carrier waveform of a first selected frequency comparable to an average migration time of photons scattered in tissue on paths from an optical input port to an optical detection port; a light source, operatively connected to the oscillator, adapted to generate light of a selected wavelength, intensity modulated at the first frequency, that is introduced to a subject at the input port; a photodiode detector adapted to detect, at the detection port, light of the wavelength that has migrated in the tissue of the subject between the input and detection ports, the detector producing a detection signal at the first frequency corresponding to the detected light; a second oscillator adapted to generate a carrier waveform of a second frequency that is offset on the order of 104 Hz from the first frequency; a reference mixer, connected to the first and second oscillators, adapted to generate a reference signal of a frequency approximately equal to the difference between the first and second frequencies; a mixer connected to receive signals from the second oscillator and the detection signal and adapted to convert the detection signal to the difference frequency; a phase detector, operatively connected to receive signals from the reference mixer and the converted detection signal, adapted to measure a phase shift between the introduced light and the detected light; and a processor adapted to calculate the pathlength based on the phase shift, and to determine a physiological property of the examined tissue based on the pathlength.
Preferred embodiments of these aspects may include one or more of the following features.
The spectrophotometer may further include a magnitude detector, connected to the photodiode detector, adapted to measure magnitude of the detected light, and the processor is further adapted to receive the magnitude for determination of the physiological property.
The spectrophotometer may further include a low frequency oximeter circuit, switchably connected to the source and the photodiode, adapted to determine absorption of light at the wavelength; and the processor is further adapted to receive absorption values from the oximeter circuit for determination of the physiological property.
The spectrophotometer may further include two automatic gain controls adapted to level signals corresponding to the introduced light and the detected light, both the leveled signals being introduced to the phase detector.
The photodiode detector may further include a substantially single wavelength filter.
The spectrophotometer may further include a second light source, operatively connected to the oscillator, adapted to generate light of a second selected wavelength that is intensity modulated at the first frequency, the radiation being introduced to a subject at a second input port; the photodiode detector further adapted to detect alternately, at the detection port, light of the first and second wavelengths that have migrated in the tissue of the subject between the first and the second input ports and the detection port, respectively; the phase detector further adapted to receive alternately signals corresponding to the detected first and second wavelengths; and the processor further adapted to receive alternately phase shifts from the phase detector, the phase shifts being subsequently used for determination of the physiological property of the tissue.
The spectrophotometer may further include a second light source, operatively connected to the oscillator, adapted to generate light of a second selected wavelength that is intensity modulated at the first frequency, the radiation being introduced to a subject at a second input port; a second photodiode detector adapted to detect, at a second detection port, light of the second wavelength that has migrated in the tissue of the subject between the second input port and the second detection port, respectively; a second phase detector, operatively connected to receive a reference signal and a detection signal from the third diode detector, adapted to measure a phase shift between the introduced and the detected light at the second wavelength; and the processor further adapted to receive a second phase shift at the second wavelength, the first and second phase shifts being subsequently used for determination of the physiological property of the tissue.
The two wavelength spectrophotometer may further include a third light source, operatively connected to the oscillator, adapted to generate light of a third selected wavelength that is intensity modulated at the first frequency, the radiation being introduced to a subject at a third input port; a third photodiode detector adapted to detect, at a third detection port, light of the third wavelength that has migrated in the tissue of the subject between the third input port and the third detection port, respectively; a third phase detector, operatively connected to receive a reference signal and a detection signal from the third diode detector, adapted to measure a phase shift between the introduced and the detected light at the third wavelength; and the processor further adapted to receive phase shifts from the phase detector, the first second and third phase shifts being subsequently used for determination of the physiological property of the tissue.
The two or three wavelength spectrophotometer may further include a first, a second (or a third) magnitude detector connected to the first, second (or third) photodiode detectors, respectively, the magnitude detectors being adapted to measure magnitude of the detected light at each of the wavelengths; and the processor further adapted to receive the magnitudes for determination of the physiological property of the tissue.
The light source may be a light emitting diode for generating light of a selected wavelength in the visible or infra-red range.
The photodiode detector may be a PIN diode or an avalanche diode.
The examined physiological property of the tissue may be hemoglobin oxygenation, myoglobin, cytochrome iron and copper, melanin, glucose or other.